Polycyclic aromatic alkaloids derived from marine plants and animals have been shown to exhibit a variety of biological activities. For example, plakinidines, which are pentacyclic pyrroloacridine compounds, are derived from the Vanuatuan red sponge, Plakortis, and have been shown to have antihelmintic activity in animals (U.S. Pat. No. 4,959,370).
Lymphostin is a pyrrolo[4,3,2-de]quinolin-8-amine produced by a soil bacterium which belongs to the genus Streptomyces and is suggested to have immunosuppressive activity (U.S. Pat. Nos. 5,843,955 and 6,815,449). Lymphostin has the following structure:

U.S. Pat. No. 6,815,449 describes synthetic analogs derived from lymphostin, the majority of which are modified at the 4-position of the molecule. The only variation at the 6-position of lymphostin resulted in nearly ten-fold reduction in lymphocyte inhibitory activity (compare Compound no. 1 with 27 in table 3 of U.S. Pat. No. 6,815,449).
Applicants have developed novel pyrrolo[4,3,2-de]quinolin-8-amine compounds that surprisingly show potent inhibitory activity of mTOR, a serine/threonine kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription and is thus implicated in various cancer pathways.